Atrial myocytes represent a heterogeneous population of cells. The common atrial myocyte is specialized not only as a contractile muscle cell but also as an endocrine cell secreting atrial natriuretic peptide (ANP) which has potent diuretic and hypotensive effects and inhibits renin and aldosterone secretion. DeBold, A. J. Science 230:767 (1985). Atrial myocytes thus have the machinery responsible for synthesis, processing and releasing ANP, including rough endoplasmic reticulum, free ribosomes, Golgi apparatus and atrial specific granules. Other ultrastructural details unique to atrial myocytes include absent or few transverse tubules and tremendous variation in the organization of sarcomeres, from dense and well-organized, as seen in ventricular cells, to scanty and haphazard. See Severs, N.J. Isolated adult cardiomyocytes. Piper et al. (ed.) Constituent cells of the heart and isolated cell models in cardiovascular research. Structure and metabolism. Vol. 1 Boca Raton: CRC Press, pp. 16-18 (1989). The ultrastructural characteristics of atrial myocytes, as well as their neurosecretory potential and their response to in vivo injury, differ so greatly from their ventricular and skeletal muscle counterparts, that they can be considered a different class of striated muscle cells. Techniques for culturing myocardiocytes from rats, chick, guinea pigs and cats have been established and are routinely used for cardiac muscle research. See Harary, I. et al., Exp. Cell. Res. 29:451-456 (1963); Friedman, B. J. et al., J. Nucl. Med. 28(9):1453-1460 (1987); Nakajima, T. et al., Circ. Res. 64(2):297-303 (1989); Follmer, C. H. et al., J. Physiol. 384:169-197 (1987), respectively. For example, the long term culture of adult rat myocardiocytes, which exhibit morphologic changes reminiscent of embryonic or neonatal cardiac muscle cells, has been described. Nag, A. C. et al., J. Mol. Cell. Cardiol. 15:301-317 (1983); see also Schwartzfeld, J. A. et al., J. Mol. Cell Cardiol. 13:563-575 (1981); Claycomb, W. C., J. Cell. Biol. 91:342 (1981); Cantin, M. et al., Science 214:566-579 (1981); Libby, P., J. Mol. Cell. Cardiol 16:803-811 (1984). Methods for culturing human fetal and transformed myocardial cells have also been developed. Holtz, D. S. et al., J. Cell. Biol. 108:1067-1078 (1989); Hassail, C. J. S. et al., Anat. Embryol 182:339-346 (1990); Claycomb, E. C. et al., In Vitro Cell. Dev. Biol. 25:1114-1120 (1989); Wang, Y. C. In Vitro Cell. Dev. Biol. 27A:63-74 (1991). The successful culture of human adult myocardiocytes derived from either the atrium or ventricle has not, however, been reported. See Cardiovasc. Res. No. 35 , Summer 1990 (p. 6), American Heart Association.
Since human adult tissue is of great interest due to numerous disease states, it would be desirable to provide techniques for the isolation, culture and proliferation of adult human myocardiocytes for research and clinical applications.